The goal of this work is to isolate and characterize the gene that encodes the product of the locus that is defective in individuals that suffer from a defect in the complementation group A locus of Xeroderma pigmentosum. Experiments designed to isolate this gene from the DNA of normal human cells are proposed. Specific aims are to develop an assay for DNA mediated gene transfer of normal UV resistance to Xeroderma pigmentosum recipient cells, to purify the gene using DNA mediated gene transfer as an assay, to obtain recombinant DNA clones that contain the gene, and to characterize the gene in normal humans and in individuals suffering from Xeroderma pigmentosum. The work is relevant to an understanding of gene organization and expression in human cells, to a detailed understanding of the molecular mechanisms involved in the repair of the ultraviolet light induced damage to DNA in human cells, and to problems of mutagenesis and carcinogenesis associated with exposure to sunlight.